Examining Sporadic Cancer Mutations Uncovers a Set of Genes Involved in Mitochondrial Maintenance

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dc.citation.articleNumber1009en_US
dc.citation.issueNumber5en_US
dc.citation.journalTitleGenesen_US
dc.citation.volumeNumber14en_US
dc.contributor.authorMoreno, Armandoen_US
dc.contributor.authorTaffet, Allisonen_US
dc.contributor.authorTjahjono, Elissaen_US
dc.contributor.authorAnderson, Quinton L.en_US
dc.contributor.authorKirienko, Natalia V.en_US
dc.date.accessioned2023-07-21T16:13:54Zen_US
dc.date.available2023-07-21T16:13:54Zen_US
dc.date.issued2023en_US
dc.description.abstractMitochondria are key organelles for cellular health and metabolism and the activation of programmed cell death processes. Although pathways for regulating and re-establishing mitochondrial homeostasis have been identified over the past twenty years, the consequences of disrupting genes that regulate other cellular processes, such as division and proliferation, on affecting mitochondrial function remain unclear. In this study, we leveraged insights about increased sensitivity to mitochondrial damage in certain cancers, or genes that are frequently mutated in multiple cancer types, to compile a list of candidates for study. RNAi was used to disrupt orthologous genes in the model organism Caenorhabditis elegans, and a series of assays were used to evaluate these genes’ importance for mitochondrial health. Iterative screening of ~1000 genes yielded a set of 139 genes predicted to play roles in mitochondrial maintenance or function. Bioinformatic analyses indicated that these genes are statistically interrelated. Functional validation of a sample of genes from this set indicated that disruption of each gene caused at least one phenotype consistent with mitochondrial dysfunction, including increased fragmentation of the mitochondrial network, abnormal steady-state levels of NADH or ROS, or altered oxygen consumption. Interestingly, RNAi-mediated knockdown of these genes often also exacerbated α-synuclein aggregation in a C. elegans model of Parkinson’s disease. Additionally, human orthologs of the gene set showed enrichment for roles in human disorders. This gene set provides a foundation for identifying new mechanisms that support mitochondrial and cellular homeostasis.en_US
dc.identifier.citationMoreno, Armando, Taffet, Allison, Tjahjono, Elissa, et al.. "Examining Sporadic Cancer Mutations Uncovers a Set of Genes Involved in Mitochondrial Maintenance." <i>Genes,</i> 14, no. 5 (2023) MDPI: https://doi.org/10.3390/genes14051009.en_US
dc.identifier.digitalgenes-14-01009-v2en_US
dc.identifier.doihttps://doi.org/10.3390/genes14051009en_US
dc.identifier.urihttps://hdl.handle.net/1911/114997en_US
dc.language.isoengen_US
dc.publisherMDPIen_US
dc.rightsExcept where otherwise noted, this work is licensed under a Creative Commons Attribution (CC BY) license.  Permission to reuse, publish, or reproduce the work beyond the terms of the license or beyond the bounds of Fair Use or other exemptions to copyright law must be obtained from the copyright holder.en_US
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en_US
dc.titleExamining Sporadic Cancer Mutations Uncovers a Set of Genes Involved in Mitochondrial Maintenanceen_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpublisher versionen_US
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